Mn(II) Quinoline Complex (4QMn) Restores Proteostasis and Reduces Toxicity in Experimental Models of Huntington’s Disease
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder, of the so-called minority diseases, due to its low prevalence. It is caused by an abnormally long track of glutamines (polyQs) in mutant huntingtin (mHtt), which makes the protein toxic and prone to aggregation. Many pathways of clearance of badly-folded proteins are disrupted in neurons of patients with HD. In this work, we show that one Mn(II) quinone complex (4QMn), designed to work as an artificial superoxide dismutase, is able to activate both the ubiquitin-proteasome system and the autophagy pathway in vitro and in vivo models of HD. Activation of these pathways degrades mHtt and other protein-containing polyQs, which restores proteostasis in these models. Hence, we propose 4QMn as a potential drug to develop a therapy to treat HD..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
International Journal of Molecular Sciences - 23(2022), 16, p 8936 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Marián Merino [VerfasserIn] |
|---|
| Links: |
doi.org [kostenfrei] |
|---|
| Themen: |
|
|---|
| doi: |
10.3390/ijms23168936 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
DOAJ024478997 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ024478997 | ||
| 003 | DE-627 | ||
| 005 | 20240414074334.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms23168936 |2 doi | |
| 035 | |a (DE-627)DOAJ024478997 | ||
| 035 | |a (DE-599)DOAJ4d52bbd137814954adf5b16fd32609b9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a QH301-705.5 | |
| 050 | 0 | |a QD1-999 | |
| 100 | 0 | |a Marián Merino |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mn(II) Quinoline Complex (4QMn) Restores Proteostasis and Reduces Toxicity in Experimental Models of Huntington’s Disease |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder, of the so-called minority diseases, due to its low prevalence. It is caused by an abnormally long track of glutamines (polyQs) in mutant huntingtin (mHtt), which makes the protein toxic and prone to aggregation. Many pathways of clearance of badly-folded proteins are disrupted in neurons of patients with HD. In this work, we show that one Mn(II) quinone complex (4QMn), designed to work as an artificial superoxide dismutase, is able to activate both the ubiquitin-proteasome system and the autophagy pathway in vitro and in vivo models of HD. Activation of these pathways degrades mHtt and other protein-containing polyQs, which restores proteostasis in these models. Hence, we propose 4QMn as a potential drug to develop a therapy to treat HD. | ||
| 650 | 4 | |a Mn(II) complexes | |
| 650 | 4 | |a Huntington’s disease | |
| 650 | 4 | |a polyQ toxicity | |
| 650 | 4 | |a autophagy | |
| 650 | 4 | |a proteasome | |
| 650 | 4 | |a <i<Caenorhabditis elegans</i< | |
| 653 | 0 | |a Biology (General) | |
| 653 | 0 | |a Chemistry | |
| 700 | 0 | |a María Dolores Sequedo |e verfasserin |4 aut | |
| 700 | 0 | |a Ana Virginia Sánchez-Sánchez |e verfasserin |4 aut | |
| 700 | 0 | |a Mª Paz Clares |e verfasserin |4 aut | |
| 700 | 0 | |a Enrique García-España |e verfasserin |4 aut | |
| 700 | 0 | |a Rafael P. Vázquez-Manrique |e verfasserin |4 aut | |
| 700 | 0 | |a José L. Mullor |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t International Journal of Molecular Sciences |d MDPI AG, 2003 |g 23(2022), 16, p 8936 |w (DE-627)DOAJ00014584X |x 14220067 |7 nnns |
| 773 | 1 | 8 | |g volume:23 |g year:2022 |g number:16, p 8936 |
| 856 | 4 | 0 | |u https://doi.org/10.3390/ijms23168936 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/4d52bbd137814954adf5b16fd32609b9 |z kostenfrei |
| 856 | 4 | 0 | |u https://www.mdpi.com/1422-0067/23/16/8936 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/1661-6596 |y Journal toc |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/1422-0067 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 951 | |a AR | ||
| 952 | |d 23 |j 2022 |e 16, p 8936 | ||